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A strong promoter activity of pre-B cell stage-specific Crlz1 gene is caused by one distal LEF-1 and multiple proximal Ets sites

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Molecules and Cells

Abstract

The promoter of pre-B cell stage-specific Crlz1 gene, whose protein translocates the cytoplasmic core binding factor β (CBFβ) into the nucleus and thereby allows its heterodimerization with Runx, has a very strong activity, which is about 25% of cytomegalovirus (CMV) promoter activity and comparable to the EF-1α promoter activity. Its transcription start site was mapped at 155 nt upstream of translation initiation codon. 5′-truncation analysis of charged amino acids rich leucine zipper 1 (Crlz1) promoter revealed that one distal region from −612 to −536 and one proximal region from −198 to −100 as numbered from the transcription start site were critical for the promoter activity. The 3′-truncation analysis of the promoter revealed that the basal promoter sequence around the transcription start site, which should be necessary for the assembly of transcription initiation complex and the start of RNA polymerase II, was also essential, although not sufficient by itself. When transcription factor binding sites within those two critical regions were searched by in vivo footprinting, one distal LEF-1 and multiple proximal Ets consensus-like sites were found to be footprinted. Indeed, the protein causing a footprint over the distal region was found to be LEF-1, and the ones causing three footprints over the proximal region were found to be such Ets family members as Fli-1 and GABP, as verified by EMSA and ChIP analyses. Furthermore, those LEF-1 and Ets sites were shown to drive additively a strong transcription of Crlz1 gene.

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References

  • Bernstein, K.A., and Baserga, S.J. (2004). The small subunit processome is required for cell cycle progression at G1. Mol. Biol. Cell 15, 5038–5046.

    Article  PubMed  CAS  Google Scholar 

  • Cho, S.-J., and Kang, C.-J. (2005). A Stat5-overlapping site is critical for the IgJ enhancer activity in the plasma cells and bound by a ubiquitous protein. Biochem. Biophys. Res. Commun. 338, 1897–1905.

    Article  PubMed  CAS  Google Scholar 

  • Crawford, H.C., Fingleton, B., Gustavson, M.D., Kurpios, N., Wagenaar, R.A., Hassell, J.A., and Matrisian, L.M. (2001). The PEA3 subfamily of Ets transcription factors synergizes with β-Catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. Mol. Cell. Biol. 21, 1370–1383.

    Article  PubMed  CAS  Google Scholar 

  • Gutierrez, A., Jr, Tschumper, R.C., Wu, X., Shanafelt, T.D., Eckel-Passow, J., Huddleston, P.M., III, Slager, S.L., Kay, N.E., and Jelinek, D.F. (2010). LEF-1 is a prosurvival factor in chronic lymphocytic leukemia and is expressed in the preleukemic state of monoclonal B-cell lymphocytosis. Blood 116, 2975–2983.

    Article  PubMed  CAS  Google Scholar 

  • Heo, J.S., Lee, S.-Y., and Lee, J.-C. (2010). Wnt/β-catenin signaling enhances osteoblastogenic differentiation from human periodontal ligament fibroblasts. Mol. Cells 30, 449–454.

    Article  PubMed  CAS  Google Scholar 

  • Hesse, J.E., Lieber, M.R., Gellert, M., and Mizuuchi, K. (1987). Extrachromosomal DNA substrates in pre-B cells undergo inversion or deletion at immunoglobulin V-(D)-J joining signals. Cell 49, 775–783.

    Article  PubMed  CAS  Google Scholar 

  • Juven-Gershon, T., Hsu, J.-Y., Theisen, J.W., and Kadonaga, J.T. (2008). The RNA polymerase II core promoter — the gateway to transcription. Curr. Opin. Cell Biol. 20, 253–259.

    Article  PubMed  CAS  Google Scholar 

  • Kamakaka, R.T., and Rine, J. (1998). Sir- and silencer-independent disruption of silencing in Saccharomyces by Sas10p. Genetics 149, 903–914.

    PubMed  CAS  Google Scholar 

  • Kang, C.-J., Sheridan, C., and Koshland, M.E. (1998). A stage-specific enhancer of immunoglobulin J chain gene is induced by interleukin-2 in a presecretor B cell stage. Immunity 8, 285–295.

    Article  PubMed  CAS  Google Scholar 

  • Kang, C.-J., Oh, U., and Koshland, M.E. (2000). Dynamic chromatin remodeling in the vicinity of J chain gene for the regulation of two stage-specific genes during B cell differentiation. Mol. Cells 10, 32–37.

    Article  PubMed  CAS  Google Scholar 

  • Lim, J.-H., Cho, S.-J., Park, S.-K., Kim, J., Cho, D., Lee, W.J., and Kang, C.-J. (2006). Stage-specific expression of two neighboring Crlz1 and IgJ genes during B cell development is regulated by their chromatin accessibility and histone acetylation. J. Immunol. 177, 5420–5429.

    PubMed  CAS  Google Scholar 

  • Maier, H., Ostraat, R., Parenti, S., Fitzsimmons, D., Abraham, L.J., Garvie, C.W., and Hagman, J. (2003). Requirements for selective recruitment of Ets proteins and activation of mb-1/Ig-α gene transcription by Pax-5 (BSAP). Nucleic Acids Res. 31, 5483–5489.

    Article  PubMed  CAS  Google Scholar 

  • Mosimann, C., Hausmann, G., and Basler, K. (2009). β-Catenin hits chromatin: regulation of Wnt target gene activation. Nat. Rev. Mol. Cell Biol. 10, 276–286.

    Article  PubMed  CAS  Google Scholar 

  • Park, S.-K., Lim, J.-H., and Kang, C.-J. (2009). Crlz1 activates transcription by mobilizing cytoplasmic CBFβ into the nucleus. Biochim. Biophys. Acta-Gene Regul. Mech. 1789, 702–708.

    CAS  Google Scholar 

  • Reya, T., O’Riordan, M., Okamura, R., Devaney, E., Willert, K., Nusse, R., and Grosschedl, R. (2000). Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism. Immunity 13, 15–24.

    Article  PubMed  CAS  Google Scholar 

  • Sakuma, T., Li, Q.-L., Jin, Y., Choi, L.-W., Kim, E.-G., Ito, K., Ito, Y., Nomura, S., and Bae, S.-C. (2001). Cloning and expression pattern of a novel PEBP2β-binding protein (charged amino acid rich leucine zipper-1 [Crl-1]) in the mouse. Mech. Dev. 104, 151–154.

    Article  PubMed  CAS  Google Scholar 

  • Wei, G.-H., Badis, G., Berger, M.F., Kivioja, T., Palin, K., Enge, M., Bonke, M., Jolma, A., Varjosalo, M., Gehrke, A.R., et al. (2010). Genome-wide analysis of ETS-family DNA-binding in vitro and in vivo. EMBO J. 29, 2147–2160.

    Article  PubMed  CAS  Google Scholar 

  • Xu, L., and Komatsu, M. (2009). Promoter cloning and characterization of the anti-vascular proliferation gene, R-ras: role of Ets- and Sp-binding motifs. J. Biol. Chem. 284, 2706–2718.

    Article  PubMed  CAS  Google Scholar 

  • Xue, H.-H., Bollenbacher-Reilley, J., Wu, Z., Spolski, R., Jing, X., Zhang, Y.-C., McCoy, J.P., and Leonard, W.J. (2007). The transcription factor GABP is a critical regulator of B lymphocyte development. Immunity 26, 421–431.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Chang-Joong Kang.

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Park, SK., Son, Y. & Kang, CJ. A strong promoter activity of pre-B cell stage-specific Crlz1 gene is caused by one distal LEF-1 and multiple proximal Ets sites. Mol Cells 32, 67–76 (2011). https://doi.org/10.1007/s10059-011-1031-5

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  • DOI: https://doi.org/10.1007/s10059-011-1031-5

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